Drug-like compound stops thyroid overstimulation in early NIH studies

Dec 01, 2010

Researchers at the National Institutes of Health have identified a compound that prevents overproduction of thyroid hormone, a finding that brings scientists one step closer to improving treatment for Graves' disease.

In Graves' disease, the thyroid gland never stops. Thyroid-stimulating antibodies bind to receptors, activating them to keep the thyroid hormone coming and coming  like a broken traffic light stuck on green  and causing the body problems in regulating energy, controlling other hormones and maintaining cells throughout the body.

Attacking the problem at its root cause, lead researcher Susanne Neumann, Ph.D., and her colleagues at the NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) have identified a chemical compound that binds to the receptors and acts as an antagonist, keeping the stimulating antibodies from their work and potentially allowing the thyroid cells to revert to normal function.

The findings, published this month in the Journal of Clinical Endocrinology and Metabolism, establish the effect of the receptor antagonist on human thyroid cells. The antagonist has not yet been tested in animals or people and still has multiple steps of toxicology and safety testing before it may be ready for human trials.

Though treatments are available for hyperthyroidism caused by Graves' disease, including surgery, radioactive iodine, and antithyroid drugs, the relapse rates for these treatments are 5 percent, 21 percent and 40 percent, respectively, and each comes with unfavorable side effects.

"Our goal is to develop an easily produced, orally administered, safe and effective drug with few to no side effects that can be used in place of some of the more invasive treatments of hyperthyroidism caused by Graves' disease," said Marvin Gershengorn, M.D., chief of the Laboratory of Endocrinology and Receptor Biology within NIDDK's intramural research program and the senior author on the paper.

Graves' disease is an autoimmune disorder, causing the body's immune system to act against the body's own cells and organs. Graves' disease typically first occurs in people under 40 and affects approximately 1 percent of the U.S. population, with women five to 10 times more likely than men to have Graves' disease.

The newly discovered compound, which is a receptor antagonist, may have the added benefit of helping those with eye problems caused by Graves' disease  called Graves' ophthalmopathy  experienced by more than 25 percent of people with the disease. Eye problems may include painful swelling in the eye sockets, double vision, tears or itchy eyes, and protruding eyes with swollen eyelids that can't be easily shut, increasing the risk for eye diseases. Because the swelling in the eyes is thought to be associated with the same overstimulation of receptors caused by the same thyroid-stimulating antibodies as in the thyroid, the potential thyroid treatment may have the added benefit of treating the eye problems as well.

The Gershengorn team is also at work on the flip side of thyroid regulation. By researching the thyroid-stimulating hormone receptor, they're hoping to use drug-like compounds to stimulate this receptor to treat people with thyroid cancer, who need more stimulation of thyroid cancer cells to increase the efficacy of iodine radiation. They've tested their discovery in mice and hope to perform pre-clinical studies and to develop human trials in the foreseeable future.

Related Stories

A cell type that causes significant scarring in lung disease appears to have a similar effect in Graves' disease, University of Michigan Health System researchers have found. The cells, called fibrocytes, are present at a ...

Vietnam War-era veterans exposed to Agent Orange appear to have significantly more Graves' disease, a thyroid disorder, than veterans with no exposure, a new study by endocrinologists at the University at Buffalo has shown.

In addition to its strong associations with hypertension, cardiovascular disease, and diabetes, pediatric obesity may induce alterations in thyroid function and structure, according to a new study accepted for publication ...

Cigarette smoking during pregnancy is associated with potentially harmful changes in both maternal and fetal thyroid function, according to a new study accepted for publication in The Endocrine Society's Journal of Clinical En ...

Thyroid hormone deficiencies in early pregnancy can cause locomotor underdevelopment in the child, according to research from the Swedish medical university Karolinska Institutet. The results bring new insights into brain ...

Pregnant women with antibodies that can indicate early thyroid disease are three times as likely to have placental separation during labor, researchers at UT Southwestern Medical Center have found in a study of more than ...

Recommended for you

New assays can detect malaria parasites in human blood at very low levels and might be helpful in the campaign to eradicate malaria, reports a study published this week in PLOS Medicine. An international team l ...

Gastric bypass and similar stomach-shrinking surgeries are a popular option for obese patients looking to lose weight or treat type 2 diabetes. While the surgeries have been linked to a decreased risk in many types of cancers, ...

Two hearts, said Keats, can beat as one; but a study led by Weizmann Institute scientists in collaboration with researchers from the University of Pennsylvania shows that sometimes a single heart muscle cell ...

New research from the University of Virginia School of Medicine has shed light on how chronic stress and obesity may contribute to type 2 diabetes. The findings point the finger at an unexpected biological perpetrator – ...

Collaborating with scientists from New York, Toronto, and Tokyo, Harvard Stem Cell Institute (HSCI) researchers have devised two methods for using stem cells to generate the type of neurons that help regulate ...

Treatment for painful episodes of blood vessel obstruction in sickle cell anemia is currently limited to controlling pain, but an investigational therapy might be able to interfere with the underlying cause of these events, ...

User comments : 0

Please sign in to add a comment.
Registration is free, and takes less than a minute.
Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.

Javascript is currently disabled in your web browser. For full site functionality, it is necessary to enable Javascript.
In order to enable it, please see these instructions.